ArticleJournal of cancer research and clinical oncology2009
Simultaneous inhibition of mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways augment the sensitivity to actinomycin D in Ewing sarcoma.
Article in Journal of cancer research and clinical oncology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Targeted and molecular therapies in Ewing sarcoma: a comprehensive review of preclinical and clinical advances.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Bioinformatic Analysis of Recurrent Genomic Alterations and Corresponding Pathway Alterations in Ewing Sarcoma.Journal of personalized medicine · 2023Article
- miR-185 suppresses progression of Ewing's sarcoma via inhibiting the PI3K/AKT and Wnt/β-catenin pathways.OncoTargets and therapy · 2018Article
- Targeting protein kinases to reverse multidrug resistance in sarcoma.Cancer treatment reviews · 2016Review
- PRAS40 deregulates apoptosis in Ewing sarcoma family tumors by enhancing the insulin receptor/Akt and mTOR signaling pathways.American journal of cancer research · 2016Article
- Primary paraesophageal Ewing's sarcoma: an uncommon case report and literature review.OncoTargets and therapy · 2015Article
- Akt and Hippo Pathways in Ewing's Sarcoma Tumors and Their Prognostic Significance.Journal of Cancer · 2015Article
- MiR-125b inhibits cell biological progression of Ewing's sarcoma by suppressing the PI3K/Akt signalling pathway.Cell proliferation · 2014Article
- EWS/ATF1 expression induces sarcomas from neural crest-derived cells in mice.The Journal of clinical investigation · 2013Article
- Dissecting the PI3K Signaling Axis in Pediatric Solid Tumors: Novel Targets for Clinical Integration.Frontiers in oncology · 2013Article
- Article
- Ewing's sarcoma: overcoming the therapeutic plateau.Discovery medicine · 2012Article
- Inhibition of lung cancer growth: ATP citrate lyase knockdown and statin treatment leads to dual blockade of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/AKT pathways.Journal of cellular physiology · 2012Article
- MAPK/ERK Signaling in Osteosarcomas, Ewing Sarcomas and Chondrosarcomas: Therapeutic Implications and Future Directions.Sarcoma · 2012Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeEwing sarcoma cells, of which over 85% retain chimeric fusion gene EWS/Fli-1, are by and large more resistant to chemotherapeutics compared to nonneoplastic cells. The purpose of this study is to determine the role of EWS/Fli-1 fusion and its downstream targets regarding the cells' resistance against actinomycin D (ActD), which is one of the most commonly used antitumor agents in combination chemotherapy of Ewing sarcomas.
methodsCytotoxicity was measured by WST-8 assay. Caspase-dependent and -independent cell death was examined by fluorescence microscope. Protein expression was analyzed by western blotting. Caspase activity was determined by Caspase-Glo assay.
resultsActD-induced caspase-dependent apoptotic cell death to Ewing sarcoma TC-135 cells in a dose- and time- dependent manner. Knockdown of EWS/Fli-1 fusion by siRNA resulted in enhancement of ActD-induced apoptosis. ActD treatment activated both mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways although in a distinctive manner. Combined administration of U0126 (MEK inhibitor) and LY294002 (PI3K inhibitor) significantly enhanced ActD-induced apoptosis in vitro and suppressed xenograft tumor growth in vivo.
conclusionsThe present study demonstrated for the first time that combination of U0126 and LY294002 can augment the cytotoxicity of ActD against Ewing sarcoma cells in vitro and in vivo. Our results indicate that further study on combination of conventional chemotherapies with MEK and PI3K inhibitors may be considered for innovative treatments of Ewing sarcoma patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.